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Gastrointestinal Imaging |
1 From the Departments of Radiology (R.M., M.G.B., G.M., A.V., P.M.) and Surgery (G.C.), A. Gemelli University Hospital, 8 Largo A. Gemelli, Rome, Italy 00168; and the Department of Radiological Sciences (C.C.), G. D'Annunzio University, Chieti, Italy. Received November 30, 1998; revision requested December 30; final revision received June 14, 1999; accepted July 20. Address reprint requests to R.M. (e-mail: rmanfredi@rm.unicatt.it).
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Abstract |
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 TOP Abstract IntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: Thirty-one patients (group 1) with chronic pancreatitis and 84 patients (group 2) with clinical and/or laboratory findings suggestive of pancreatic disease who did not have ductal alterations at ultrasonography (US) and/or computed tomography (CT) underwent MRCP before and up to 10 minutes after secretin stimulation. Size of the main pancreatic duct (head, body, tail) and duodenal filling before and after secretin stimulation were measured quantitatively. Image quality, number of main pancreatic ductal segments visualized, visualization of side branches, ductal narrowing, endoluminal filling defects, and presence of pancreas divisum were analyzed qualitatively.
RESULTS: In both groups, the size of the main pancreatic duct increased significantly 3 minutes after secretin stimulation. Reduced duodenal filling was detected in patients with severe chronic pancreatitis (P < .001). The number of segments of the main pancreatic duct visualized improved from 85 (91%) to 93 (100%) of 93 in group 1 and from 164 (65%) to 245 (97%) of 252 (P < .001) in group 2. Visualization of side branches improved from 22 (71%) to 31 (100%) of 31 in group 1 and from three (4%) to 53 (63%) of 84 (P < .001) in group 2. Pancreas divisum was visualized in one additional patient in group 1 and in six additional patients in group 2.
CONCLUSION: The administration of secretin improves visualization of the pancreatic ducts and helps in the evaluation of exocrine reserve.
Index terms: Endoscopic retrograde cholangiopancreatography (ERCP) • Magnetic resonance (MR), rapid imaging, 73.121416, 770.121416 • Pancreas, function • Pancreas, MR, 770.121411, 770.121412, 770.121415 • Pancreatic ducts, MR, 774.121416, 774.297, 774.921 • Pancreatitis, 774.291 • Secretin
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Endoscopic retrograde cholangiopancreatography (ERCP) is currently the method of choice for the evaluation of patients with chronic pancreatitis because it shows ductal abnormalities that confirm the clinical diagnosis. ERCP provides ductal anatomic mapping for pretherapeutic evaluation and interventional procedures such as stricture dilation, placement of stents, stone removal, biopsy, or brushing. It is also used to depict communication with a pancreatic pseudocyst (2). In addition, ERCP is helpful in the assessment of exocrine functional reserve; this is accomplished by means of pancreatic fluid collection after stimulation with secretin (3).
ERCP, however, is expensive and invasive, with a reported complication rate of 5% (4). Furthermore, in up to 30% of the cases, inadequate opacification of the pancreatic duct results in an incomplete examination (5).
Magnetic resonance (MR) cholangiopancreatography (MRCP) is a noninvasive imaging modality that accurately and simultaneously depicts the morphologic abnormalities of the biliary and pancreatic ducts and parenchymal structures (6–13). However, visualization of normal or minimally dilated pancreatic ducts at MRCP is more challenging because these ducts are smaller than those of the biliary tree (14). In a previous study (15), MRCP findings agreed with ERCP findings in 70%–92% of the patients evaluated for pancreatic ductal abnormalities. The agreement, however, tended to be worse in the tail of the duct, and minimally dilated side branches were not routinely recognized; this led to a high false-negative rate. The recent development of half-Fourier pulse sequences and phased-array surface coils enables the acquisition of high-quality MR cholangiopancreatograms during breath holding, with a high signal-to-noise ratio (16).
The exogenous administration of secretin stimulates the secretion of fluids and bicarbonates by the exocrine pancreas, with a consequent increase in the volume of fluids inside the pancreatic ducts (17). This increase in size and fluid content has already been used to improve the visualization of the pancreatic ducts at ultrasonography (US) (18–20). The exogenous administration of secretin also improves visualization of the pancreatic ducts at MRCP (21–24). Furthermore, functional studies on the exocrine pancreas can be performed by combining rapid imaging and the administration of secretin.
The aim of our study was to assess whether the administration of secretin improves visualization of the pancreatic duct at MRCP in patients with severe chronic pancreatitis or suspected pancreatic disease.
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MATERIALS AND METHODS |
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Sixty-seven patients were male, and 48 were female (mean age, 45.2 years; age range, 6–75 years). The patients were asked to fast for at least 4 hours before examination. The study was approved by our hospital review board, and informed consent was obtained in all patients after the examination procedure was explained.
The patients were assigned to one of two groups for the study. Group 1 included 31 patients (23 male patients, eight female patients; mean age, 42.2 years; age range, 8–75 years) with severe chronic pancreatitis and a dilated main pancreatic duct. These were diagnosed by means of clinical history, laboratory findings, and/or previous findings at US (31 patients), CT (27 patients), and/or ERCP (19 patients). All patients in this group subsequently underwent therapeutic ERCP.
Group 2 included 84 patients (44 male patients, 40 female patients; mean age, 46.0 years; age range, 6–72 years) who were referred for suspected pancreatic disease because of abdominal pain, enzymatic abnormalities, and/or recurrent attacks of acute nonbiliary pancreatitis in the absence of evident ductal alterations at US or CT. Twenty-eight of the 84 patients in this group underwent ERCP (whereas 56 did not) and were being followed-up at the time this article was written.
MR Imaging Technique
MR studies were performed (by R.M.) with a 1.5-T imager (Signa Horizon Echospeed; GE Medical Systems, Milwaukee, Wis) with use of a phased-array coil (Thorso; GE Medical Systems).
Transverse T1-weighted gradient-echo images were obtained from the dome of the liver to the pancreas, with the following parameters: 160/4.2 (repetition time msec/echo time msec); flip angle, 90°; section thickness, 8 mm; intersection gap, 1 mm; matrix, 256 x 192; number of signals acquired, one; field of view, 40 cm; and total acquisition time, 24 seconds. Transverse T2-weighted single-shot fast spin-echo images were obtained from the dome of the liver to the pancreas, with the following parameters: 
/110; section thickness, 8 mm; intersection gap, 1 mm; matrix, 256 x 256; number of signals acquired, one-half; field of view, 40 cm; and total acquisition time, 27 seconds.
Transverse T1-weighted fat-saturated gradient-echo images were subsequently obtained, only in the pancreas, with the following parameters: 160/4.2; flip angle, 90°; section thickness, 6 mm; intersection gap, 1 mm; matrix, 256 x 192, number of signals acquired, one; field of view, 30 cm; and total acquisition time, 24 seconds. Transverse T2-weighted single-shot fast spin-echo images were also obtained in the pancreas, with the following parameters: /110; section thickness, 6 mm; intersection gap, 1 mm; matrix, 256 x 256; number of signals acquired, one-half; field of view, 30 cm; and total acquisition time, 24 seconds.
MRCP was performed with a dynamic, breath-hold, two-dimensional, heavily T2-weighted, single-shot fast spin-echo sequence in the coronal plane. The following parameters were used: /800–1,400; section thickness, 35–45 mm; matrix, 256–512 x 256; number of signals acquired, one-half; field of view, 26–35 cm; and total acquisition time, 2 seconds. By using these parameters, only stationary fluids were depicted on the MR images, whereas the signal of the solid organs decayed away. No postprocessing was performed.
To eliminate the overlap of fluid-containing organs, a negatively charged contrast agent consisting of 200 mL of superparamagnetic iron oxide particles (Lumirem [ferumoxsil]; Guerbet, Aulnay-sou-Bois, France) was orally administered before dynamic imaging.
A set of MRCP images was acquired before the administration of secretin to optimally position the image section; the sections included the entire main pancreatic duct and its emergence in the papilla. After the intravenous administration of secretin (Sekretolin; Hoechst, Frankfurt am Main, Germany) in a dose of 1 clinical unit per kilogram of body weight, acquisition of the optimal section was repeated every 30 seconds. The dynamic procedure was conducted in 10 minutes, and the overall examination time was 30–35 minutes. No image postprocessing was performed.
According to the findings from a previous study (21), the density of the pancreatic fluid and that of a superparamagnetic nanoparticulate suspension are different, and the two liquids may coexist without mixing. Therefore, undesired signal intensity reduction in the duodenum may be avoided. Duodenal filling with pancreatic secretion was evaluated as an indirect parameter of the pancreatic functional reserve.
Image Analysis
The quantitative image analysis included two parts. First, the size of the main pancreatic duct was measured before secretin stimulation and at 1, 3, 5, and 10 minutes afterward. Measurements were obtained with an electronic caliper in the head, body, and tail of the pancreatic duct by a radiologist (M.G.B.) who did not perform the qualitative analysis. Second, the secretion of pancreatic fluid was semiquantitatively evaluated on the dynamic images according to the methods described by Matos et al (21). The volume of duodenal filling was graded as follows: 0, no fluid was observed in the duodenum; 1, fluid was limited to the duodenal cap; 2, fluid filled the duodenal cap and partially filled the duodenum up to the genu inferius (angle between the descending and horizontal parts of the duodenum); or 3, the duodenum was largely filled with fluid beyond the genu inferius.
MRCP images were independently analyzed by three of the authors (R.M., G.C., C.C.) who were experienced in biliary and pancreatic imaging. They were blinded to the clinical data; interpretation discrepancies were resolved by consensus. Qualitative image analysis included an overall evaluation of image quality as follows: poor, anatomic parts were difficult to assess; sufficient, anatomic parts were partially visible; and good, whole anatomic parts were visible. Improvement in image quality after secretin stimulation was subjectively assessed by using the following three-point scale: 1, no improvement; 2, slight improvement in the visualization of the pancreatic duct; and 3, major improvement in the visualization of the pancreatic duct. Other parameters assessed before and after the administration of secretin were the following: number of segments of the main pancreatic duct visualized (head, body, tail), visualization of side branches, presence of ductal narrowing, endoluminal filling defects, and presence of pancreas divisum.
Statistical Analysis
A model for the analysis of the variance, or ANOVA, for repeated measurements was applied to analyze the increase in size of the main pancreatic duct before and after secretin stimulation in the head, body, and tail of the pancreas in each group. A Student t test was subsequently applied to analyze the difference between the size of the main pancreatic duct before and 3 minutes after secretin stimulation in the head, body, and tail of the pancreas in the two groups. In addition, a Wilcoxon signed rank test was performed to compare the number of main pancreatic ductal segments and side branches visualized before and after secretin stimulation in the two groups. A Mann-Whitney U test was applied to compare duodenal filling after secretin stimulation in the two groups.
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RESULTS |
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The number of segments of the main pancreatic duct detected before secretin stimulation was 85 (91%) of 93, whereas, afterward, the number of segments detected improved to 93 (100%). The difference, however, was not significant (Table). Side branches were detected in 22 (71%) of the 31 patients before the administration of secretin, whereas afterward, side branches were detected in 31 (100%) patients. The improvement, however, was not significant. Ductal narrowing was detected in 21 (68%) of the 31 patients before the administration of secretin and in 27 (87%) patients afterward (Table, Fig 2). Endoluminal filling defects were observed in 18 (58%) of the 31 patients before the administration of secretin and in 20 (65%) patients afterward (Fig 4). The presence of pancreas divisum was detected in one patient (3%) before secretin and in two (6%) patients afterward (Table).
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Qualitative image analysis.—Before secretin stimulation, the overall quality of the MR cholangiopancreatograms was considered to be poor in 33 (39%) of the 84 patients, sufficient in 35 (42%) patients, and good in 16 (19%) patients. After secretin stimulation, the overall image quality was rated as poor in four (5%) of the 84 patients, sufficient in 24 (29%), and good in 56 (67%). Improvement in the image quality for the visualization of the pancreatic ducts after secretin stimulation was subjectively rated as 1 (no improvement) in 34 (40%) of the 84 patients, as 2 (slight improvement) in 33 (39%) patients, and as 3 (major improvement) in 17 (20%) patients.
The number of segments of the main pancreatic duct detected before secretin stimulation was 164 (65%) of 252 segments, whereas, afterward, the number of segments visualized increased significantly to 245 (97%, P < .001) (Table). Seven pancreatic segments were never visualized before or after the administration of secretin because of the presence of an adjacent fluid-filled structure (4 segments) and because of the lack of ductal filling (3 segments).
Side branches were observed in three (4%) of the 84 patients before the administration of secretin, whereas afterward, side branches were detected in 53 (63%) patients (P < .001). Ductal narrowing was detected in three (4%) of the 84 patients before secretin stimulation, whereas afterward, it was detected in nine (11%) patients (Table, Fig 7). Endoluminal filling defects were detected in none of the patients before the administration of secretin and in three (4%) patients afterward. Pancreas divisum was detected in six (7%) of the 84 patients before the administration of secretin and in 12 (14%) patients afterward (Table).
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The recent introduction of half-Fourier pulse sequences and phased-array surface coils enables the acquisition of MRCP images during breath holding, with high signal-to-noise ratio. This allows the noninvasive visualization of pancreatic ducts (16). Comparative studies with ERCP have been performed (15). A limitation of MRCP is an occasional difficulty in the visualization of the side branches and tail of the pancreas (15); alterations of these are indicative of early chronic pancreatitis.
The intravenous administration of secretin stimulates the exocrine pancreatic parenchyma, with an accumulation of fluid and bicarbonates in the ductal system. This effect has been used by some authors (18–20) to improve visualization of the main pancreatic duct at US. However, at US, it may be difficult to visualize all of the segments of the main pancreatic duct in a consistent and reproducible manner. The administration of secretin at MRCP also improves the visualization of the pancreatic duct because of an increase in ductal caliber and an increase in the fluid content, which improves the signal-to-noise ratio (Fig 6) (21).
We assessed the role of secretin in improving the visualization of the pancreatic ducts in patients with severe chronic pancreatitis or suspected pancreatic disease. The combination of the increased mean caliber of the ducts and the improved signal-to-noise ratio reduced, in our study, the number of poor-quality MR cholangiopancreatograms that were obtained after the administration of secretin. The number of poor-quality images was reduced from one to none of 31 in group 1 (patients with diagnosed severe chronic pancreatitis) and from 33 to four of 84 in group 2 (patients with suspected pancreatic disease). There was also a slight to major subjective image quality improvement in 14 (45%) of the 31 patients in group 1 and in 50 (60%) of the 84 patients in group 2.
An enlarged main pancreatic duct with dilated side branches is the most frequent sign detected in patients with severe chronic pancreatitis (25). In our study, these patients had, before secretin stimulation, a caliber in all segments of the main pancreatic duct was larger than that of the segments in patients with suspected pancreatic disease (Fig 1). In addition, the progressive tapering pattern of the pancreatic duct, which normally proceeds toward the tail of the gland, was lost in patients with severe chronic pancreatitis.
In our series, the difference in the size of the duct in the head and body of the pancreas was not significant. Despite this baseline ductal enlargement, there was a significant increase in size 3 minutes after the administration of secretin, especially in the head and body of the pancreas (Fig 1). In patients with suspected pancreatic disease, the size of all segments of the main pancreatic duct increased significantly 3 minutes after the administration of secretin (P < .001); this probably indicated a preserved elastic capacity of pancreatic tissues (Fig 5).
Duodenal filling observed after secretin stimulation can be used to semiquantitatively evaluate pancreatic secretion, which is an indirect index of pancreatic exocrine reserve. An evaluation of this reserve may be important because it can be used to establish the clinical diagnosis and to monitor the disease and its response to treatment. Exocrine function can be evaluated by the use of noninvasive indirect tests, such as the bentiromide test or pancreolauryl test (26), or invasive direct tests, such as the secretin-cholecystokinin test or secretin-cerulein test, which require intubation of the duodenum and eventual cannulation of the main pancreatic duct (27).
In our series, patients with severe chronic pancreatitis showed duodenal filling that was significantly less than that of patients with suspected chronic pancreatitis (P < .001). In group 1, 20 (65%) of 31 patients had duodenal filling of grades 0–2, compared with 12 (14%) of 84 patients in group 2. This probably reflects a reduced pancreatic exocrine reserve in the advanced phase of the disease (Figs 2, 3).
Because of the dilatation of the pancreatic ducts, which is typically found in patients with severe chronic pancreatitis, 85 (91%) of the 93 segments of the main pancreatic duct (head, body, tail) and 22 (71%) of the 31 dilated side branches were detected before the administration of secretin (Table). Therefore, in the majority patients with severe chronic pancreatitis, the pancreatic ducts can be assessed without secretin stimulation. After secretin stimulation, visualization of both the main pancreatic ductal segments and side branches improved. The difference, however, was not significant. Therefore, in this group of patients, visualization and subsequent evaluation of the pancreatic ducts was less dependant on the administration of secretin.
In patients with suspected pancreatic disease, the main pancreatic duct most frequently has a normal size. In this group of patients, visualization at MRCP may be difficult, especially in the tail of the gland; this may limit information about the morphology of the duct. In our series, the administration of secretin increased the number of main pancreatic ductal segments visualized from 164 (65%) to 245 (97%) of 252 segments (Table). This permitted a more extensive evaluation of the pancreatic ducts.
The hallmark finding in the diagnosis of early chronic pancreatitis at ERCP is dilatation of the side branches. Because of their small size, MRCP is not able to routinely depict dilated side branches; this leads to a high false-negative rate (15). In our series, the improved visualization of the side branches (from three [4%] to 53 [63%] of the 84 patients) at MRCP after secretin stimulation will probably help in the diagnosis of early chronic pancreatitis and reduce the false-negative rate (Figs 5, 7). In this group, early chronic pancreatitis was diagnosed in 19 of 28 patients who underwent ERCP. Improved visualization of the dilated side branches makes MRCP with secretin stimulation a promising alternative to diagnostic ERCP; the endoscopic approach would be indicated only for therapeutic purposes.
Ductal filling due to pancreatic secretion after secretin stimulation also improved visualization of ductal narrowing and endoluminal filling defects (Table, Fig 4). This improvement, however, was not significant in patients in group 1 most likely because the duct was already large before the administration of secretin. However, the dynamic assessment obtained at rapid imaging after the administration of secretin is important because it gives information about the hydrodynamic changes caused by strictures, endoluminal stones, and/or proteic plugs. This is helpful in the assessment of lesional features (hydrodynamic significance, length, position) and in the planning of adequate treatment, such as interventional ERCP and/or lithotripsy.
The prevalence of ductal narrowing and endoluminal filling defects was low in patients with suspected pancreatic disease (Table). However, MRCP with secretin stimulation resulted in improved visualization of these alterations. Ductal narrowing was detected in three (4%) of the 84 patients before secretin stimulation and in nine (11%) patients afterward. Similarly, endoluminal filling defects were detected in none of the patients before the administration of secretin and in three patients afterward.
Pancreas divisum, a congenital abnormality that results from the failure of the dorsal and ventral ducts to fuse during organogenesis, has a prevalence of 12% (19 of 154) at MRCP (28). Besides pancreas divisum, other anatomic variants allow egression of the major fraction of pancreatic secretions via the dorsal ductal orifice. These variants, which are characterized by a dominant dorsal duct, are found in nearly 10% of the population; this prevalence is double that of pancreas divisum (29). In our series, dynamic MRCP after secretin stimulation helped in the detection of these ductal variants (one additional patient in group 1 and six additional patients in group 2) (Table) and in the planning of adequate treatment (29).
The use of secretin slightly increases the cost of the MR examination because of the cost of the secretin itself and because it prolongs the MR imaging time by 10–15 minutes. However, in our institution, we are observing an initial trend toward a reduction in the number of diagnostic ERCP examinations performed, with the advent of MRCP with secretion stimulation; this reduces costs in providing patient care. Therefore, in the diagnostic algorithm for patients with severe chronic pancreatitis and for patients suspected of having pancreatic disease who do not have evidence of disease at US and/or CT, secretin should always be administered to enhance the capabilities of MRCP.
In conclusion, our study findings show that patients with severe chronic pancreatitis had a dilatation of the main pancreatic duct and side branches before secretin stimulation. Therefore, visualization and subsequent evaluation of the pancreatic ducts at MRCP is less dependant on the administration of secretin. Furthermore, the patients with severe chronic pancreatitis showed a significant reduction in duodenal filling compared with that of the patients suspected of having pancreatic disease. This most likely indicates a reduced pancreatic exocrine reserve.
Improved visualization of the side branches at MRCP with secretin stimulation will probably allow an earlier diagnosis of chronic pancreatitis and reduce the false-negative rate of MRCP to make it a valid, noninvasive alternative to diagnostic ERCP in patients suspected of having pancreatic disease.
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Footnotes |
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Author contributions: Guarantor of integrity of entire study, P.M.; study concepts, A.V., G.C.; study design, A.V.; definition of intellectual content, G.C.; literature research, R.M.; clinical studies, R.M., M.G.B.; data acquisition, R.M.; data analysis, R.M., G.C., C.C.; statistical analysis, R.M; manuscript preparation, R.M.; manuscript editing, C.C.; manuscript review, G.C., M.G.B., G.M.
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), body (
), and tail (
) of the pancreas before (0 minutes) and 1, 3, 5, and 10 minutes after the administration of secretin in patients with severe chronic pancreatitis (group 1). The size of the pancreatic duct before secretin stimulation and the size 3 minutes afterward are significantly different.
